The candidate, Dr. Stark, received a B.S. in Biology from the Cleveland State University, and his Ph.D and M.D. degrees from Case Western Reserve University through the Medical Scientists Training Program. His Ph.D. Thesis described plasmid-encoded hemolysin of E. coli. Dr. Stark received clinical training in Pediatrics, and subspecialty training in Pediatric Pulmonology. The research project during his fellowship training focused on the description of the molecular biology of Parainfluenza virus type 2, and on establishing an in vitro model for viral lower respiratory tract infection. Dr. Stark joined the faculty at the University of Wisconsin in July l989 as an Assistant Professor (tenure track) in the Department of Pediatrics. In association with Dr. Busse, he has obtained the preliminary data presented and developed the proposed project. The hypothesis for the proposed project is that viral infection of the lower airway causes the expression of new or altered surface molecules (proteins) on the airway epithelium which are recognized by inflammatory cells, resulting in the "priming" or activation of these cells. The expression of these antigens is, therefore, the pivotal step in subsequent airway injury and airway smooth muscle hyperreactivity. This hypothesis is supported by preliminary studies presented here that demonstrate neutrophil and eosinophil recognition of infected airway epithelium. The research project focuses on the interactions between viral glycoproteins expressed on human airway epithelial cells and airway inflammatory cells (neutrophils and eosinophils). The genes for the glycoproteins will be cloned into an expression vector and transfected into an immortalized epithelial cell line. The following measures of cellular interactions will be studied: 1) attachment; 2) cell activation, mediator production, and mediator release; 3) target cell killing. In summary, these studies will use the infection model to investigate the interaction of infected airway epithelial cells with neutrophils and eosinophils and determine the relationship of this interaction to the epithelial pathology. The Department of Pediatrics and Medicine at the University of Wisconsin have longstanding commitments to research. The candidate's sponsor, Dr. William Busse (Professor and Head of the Allergy and Clinical Immunology Section at the UW-Madison), has a longstanding interest and recognized expertise in asthma and the eosinophil, and has several NIH grants dealing with the viral infections and asthma. The candidate's co-sponsor, Dr. Philip Farrell (Chairman of the Department of Pediatrics), has a strong background in basic science research and a long-term commitment to establishing research programs in this department. The candidate is assured protected time and facilities for the proposed project.